Abstract
Escherichia coli (E. coli) K1 causes meningitis and remains an unsolved problem in neonates, despite the application of antibiotics and supportive care. The cross-reactivity of bacterial capsular polysaccharides with human antigens hinders their application as vaccine candidates. Thus, protein antigens could be an alternative strategy for the development of an E. coli K1 vaccine. Outer membrane protein A (OmpA) of E. coli K1 is a potential vaccine candidate because of its predominant contribution to bacterial pathogenesis and sub-cellular localization. However, little progress has been made regarding the use of OmpA for this purpose due to difficulties in OmpA production. In the present study, we first investigated the immunogenicity of the four extracellular loops of OmpA. Using the structure of OmpA, we rationally designed and successfully generated the artificial protein OmpAVac, composed of connected loops from OmpA. Recombinant OmpAVac was successfully produced in E. coli BL21 and behaved as a soluble homogenous monomer in the aqueous phase. Vaccination with OmpAVac induced Th1, Th2, and Th17 immune responses and conferred effective protection in mice. In addition, OmpAVac-specific antibodies were able to mediate opsonophagocytosis and inhibit bacterial invasion, thereby conferring prophylactic protection in E. coli K1-challenged adult mice and neonatal mice. These results suggest that OmpAVac could be a good vaccine candidate for the control of E. coli K1 infection and provide an additional example of structure-based vaccine design.
Highlights
Escherichia coli (E. coli) K1 is a Gram-negative bacterium that commonly causes meningitis in neonates (Scheld et al, 2002)
To test the immunogenicity of the extracellular loops of Outer membrane protein A (OmpA), firstly sera from eight E. coli K1-infected patients were collected, and their contents of anti-loop antibodies were determined via ELISA
Antibodies against loop1, loop2, loop3, and loop4 were not observed in sera from the healthy control but were observed in sera from all E. coli K1-infected patients (Figure 1B)
Summary
Escherichia coli (E. coli) K1 is a Gram-negative bacterium that commonly causes meningitis in neonates (Scheld et al, 2002). This bacterium initially colonizes nasopharyngeal or gastrointestinal sites. Despite the conventional application of antibiotics and supportive care, the morbidity, and Rational Design of E. coli K1 Vaccine mortality rates of E. coli K1-associated neonatal meningitis remain unchanged (Nau et al, 2015; van de Beek et al, 2016). The fatality rates of E. coli K1-infected infants range from 5 to 30%, and the survivors often exhibit life-time sequelae, such as mental retardation, cortical blindness, and hearing loss (Croxen and Finlay, 2010; van de Beek et al, 2010). An effective vaccine is urgently needed for the effective control of E. coli K1 infection
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